Lutein attenuates rheumatoid arthritis progression by suppressing MAPK/NF-κB signaling and MMP3 and MMP13 expression in fibroblast-like Synoviocytes

Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting approximately 1 % of the global population, characterized by synovitis and joint destruction. Current therapies aim to control inflammation but often result in adverse effects or limited efficacy. Lutein is a natural carotenoid that possesses antioxidant and anti-inflammatory properties. However, the potential of lutein in mitigating the progression of RA remains unclear. In this study, we utilized dataset GSE55235, comprising transcriptomic profiles of synovial tissues from RA, OA, and healthy individuals, enabling precise discrimination of RA-specific gene signatures. Additionally, we analyzed dataset GSE1919, which contains whole-genome expression data comparing RA synovial tissues with OA and healthy donor tissues, facilitating the characterization of key pathogenic mechanisms underlying RA. Our gene expression analyses revealed significant upregulation of matrix metalloproteinases (MMPs), confirming their pivotal role in RA pathogenesis. RNA sequencing of lutein-treated fibroblast-like synoviocytes (FLS) identified differentially expressed genes, with gene set enrichment analysis indicating suppression of RA-related pathways and extracellular matrix degradation. Ingenuity Pathway Analysis demonstrated that lutein inhibits synovial invasion and cartilage destruction by downregulating MAPK and NF-κB signaling. In vitro experiments confirmed that lutein suppresses TNF-α-induced p38, ERK, and NF-κB activation, reducing MMP3 and MMP13 expression and inhibiting FLS migration. These findings were validated in a collagen-antibody-induced arthritis model, where lutein reduced synovial inflammation and joint damage. Collectively, this study highlights lutein's potential as a dietary supplement for RA management by alleviating oxidative stress, suppressing inflammatory responses, and preserving joint integrity. Further clinical studies are warranted to explore its therapeutic applications in RA treatment.